1. Cytotoxic T lymphocyte–induced killing in the absence of granzymes A and B is unique and distinct from both apoptosis and perforin-dependent lysis
- Author
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Stephen J. Turner, Nigel J. Waterhouse, Annette Ciccone, Joseph A. Trapani, Misty R. Jenkins, Vivien R. Sutton, Phillip I. Bird, and Karin A Sedelies
- Subjects
Pore Forming Cytotoxic Proteins ,Programmed cell death ,Immunology ,Apoptosis ,chemical and pharmacologic phenomena ,Cytoplasmic Granules ,Article ,Granzymes ,Pore forming protein ,Mice ,Animals ,Immunology and Allergy ,Cytotoxic T cell ,Research Articles ,Mice, Knockout ,Mice, Inbred C3H ,Membrane Glycoproteins ,Cell Death ,biology ,Perforin ,Serine Endopeptidases ,hemic and immune systems ,Cell Biology ,Cell biology ,Mice, Inbred C57BL ,Granzyme B ,Cytolysis ,CTL ,Granzyme ,biology.protein ,Cell Surface Extensions ,T-Lymphocytes, Cytotoxic - Abstract
Cytotoxic T lymphocyte (CTL)–induced death triggered by the granule exocytosis pathway involves the perforin-dependent delivery of granzymes to the target cell. Gene targeting has shown that perforin is essential for this process; however, CTL deficient in the key granzymes A and B maintain the ability to kill their targets by granule exocytosis. It is not clear how granzyme AB−/− CTLs kill their targets, although it has been proposed that this occurs through perforin-induced lysis. We found that purified granzyme B or CTLs from wild-type mice induced classic apoptotic cell death. Perforin-induced lysis was far more rapid and involved the formation of large plasma membrane protrusions. Cell death induced by granzyme AB−/− CTLs shared similar kinetics and morphological characteristics to apoptosis but followed a distinct series of molecular events. Therefore, CTLs from granzyme AB−/− mice induce target cell death by a unique mechanism that is distinct from both perforin lysis and apoptosis.
- Published
- 2006
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